Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) combined with sodium hyaluronate solution for facial microdroplet injection in improving facial skin photoaging.Methods:A prospective randomized controlled trial was conducted. From January to July 2024, patients with facial photoaging problems were recruited from the Plastic Surgery Department of the Affiliated Hospital of Xuzhou Medical University and randomly divided into a monotherapy group (sodium hyaluronate solution droplet injection) and a combination therapy group (BTX-A + sodium hyaluronate solution droplet injection) by hierarchical block randomization method. The treatment regimen was 3 months, with one treatment for each month, with a total of 3 treatment. The combination therapy group only used a combination therapy of two drugs (BTX-A 25 U+ 5 ml sodium hyaluronate solution) during the first injection. During the three treatments of the monotherapy group and the second and third treatments of the combination therapy group, 5 ml of sodium hyaluronate solution was injected as the solo ingredient. Follow up was conducted at 1, 2, and 4 months after the last treatment. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by test kit. Five skin texture indicators (moisture content, transepidermal water loss rate, elasticity, glossiness, and pH) were evaluated using the German CK skin tester. VISIA skin detector was used for facial two-dimensional photography and skin condition analysis. Clinical efficacy (significant improvement, obvious improvement, improvement, no improvement) and global aesthetic improvement scale (GAIS) scores on a 5-point scale were recorded. Patient satisfaction levels (very satisfied, satisfied, and dissatisfied) were investigated. The data were analyzed using SPSS 27.0 software. Count data was presented as examples and(or) percentages, and analyzed using a chi-square test. Normal distribution measurement data was represented by Mean±SD and analyzed using t-test. Results:A total of 100 patients were included, with 50 cases in each group. There were 17 males and 33 females in the monotherapy group, with an age of (31.3±7.1) years, and there were 5, 14, 29 and 2 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There were 15 males and 35 females in the combination therapy group, with an age of (32.1±8.4) years old, and there were 4, 15, 27 and 4 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There was no statistically significant difference in gender composition, age, and Glogau skin photoaging classification between the two groups (all P>0.05). One month after the first treatment, both groups showed an increase in SOD activity and a decrease in MDA levels, with more significant changes observed in the combination therapy group ( P<0.01 for both). At the follow-up of 1, 2, and 4 months after the last treatment, the combination therapy group outperformed the monotherapy group in all 5 skin texture indicators (all P<0.05). One month after the last treatment, the total effective rate of the combination therapy group was 76.0% (38/50), which were significantly higher than that of the monotherapy group’s 50.0% (25/50) ( P<0.05); in addition, the combination therapy group showed significant advantages in facial aesthetic GAIS scores, as well as patient satisfaction, with a satisfaction rate of up to 98.0% (49/50), which was higher than the 88.0% (44/50) of the monotherapy group ( P<0.01). Throughout the entire treatment process, neither group experienced serious adverse reactions. Conclusion:Facial microdroplet injection of BTX-A combined with sodium hyaluronate solution effectively improves symptoms of facial skin photoaging, enhancing skin hydration and elasticity, reducing transepidermal water loss, improving skin gloss, regulating skin pH, and enhancing skin antioxidant capacity, ultimately achieving facial skin rejuvenation. This method is safe, effective and holds high clinical relevence and patient satisfaction.

Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) combined with sodium hyaluronate solution for facial microdroplet injection in improving facial skin photoaging.Methods:A prospective randomized controlled trial was conducted. From January to July 2024, patients with facial photoaging problems were recruited from the Plastic Surgery Department of the Affiliated Hospital of Xuzhou Medical University and randomly divided into a monotherapy group (sodium hyaluronate solution droplet injection) and a combination therapy group (BTX-A + sodium hyaluronate solution droplet injection) by hierarchical block randomization method. The treatment regimen was 3 months, with one treatment for each month, with a total of 3 treatment. The combination therapy group only used a combination therapy of two drugs (BTX-A 25 U+ 5 ml sodium hyaluronate solution) during the first injection. During the three treatments of the monotherapy group and the second and third treatments of the combination therapy group, 5 ml of sodium hyaluronate solution was injected as the solo ingredient. Follow up was conducted at 1, 2, and 4 months after the last treatment. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by test kit. Five skin texture indicators (moisture content, transepidermal water loss rate, elasticity, glossiness, and pH) were evaluated using the German CK skin tester. VISIA skin detector was used for facial two-dimensional photography and skin condition analysis. Clinical efficacy (significant improvement, obvious improvement, improvement, no improvement) and global aesthetic improvement scale (GAIS) scores on a 5-point scale were recorded. Patient satisfaction levels (very satisfied, satisfied, and dissatisfied) were investigated. The data were analyzed using SPSS 27.0 software. Count data was presented as examples and(or) percentages, and analyzed using a chi-square test. Normal distribution measurement data was represented by Mean±SD and analyzed using t-test. Results:A total of 100 patients were included, with 50 cases in each group. There were 17 males and 33 females in the monotherapy group, with an age of (31.3±7.1) years, and there were 5, 14, 29 and 2 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There were 15 males and 35 females in the combination therapy group, with an age of (32.1±8.4) years old, and there were 4, 15, 27 and 4 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There was no statistically significant difference in gender composition, age, and Glogau skin photoaging classification between the two groups (all P>0.05). One month after the first treatment, both groups showed an increase in SOD activity and a decrease in MDA levels, with more significant changes observed in the combination therapy group ( P<0.01 for both). At the follow-up of 1, 2, and 4 months after the last treatment, the combination therapy group outperformed the monotherapy group in all 5 skin texture indicators (all P<0.05). One month after the last treatment, the total effective rate of the combination therapy group was 76.0% (38/50), which were significantly higher than that of the monotherapy group’s 50.0% (25/50) ( P<0.05); in addition, the combination therapy group showed significant advantages in facial aesthetic GAIS scores, as well as patient satisfaction, with a satisfaction rate of up to 98.0% (49/50), which was higher than the 88.0% (44/50) of the monotherapy group ( P<0.01). Throughout the entire treatment process, neither group experienced serious adverse reactions. Conclusion:Facial microdroplet injection of BTX-A combined with sodium hyaluronate solution effectively improves symptoms of facial skin photoaging, enhancing skin hydration and elasticity, reducing transepidermal water loss, improving skin gloss, regulating skin pH, and enhancing skin antioxidant capacity, ultimately achieving facial skin rejuvenation. This method is safe, effective and holds high clinical relevence and patient satisfaction.

Mesenchymal stem cell (MSC)-derived exosomes (Exos) were reported to a prospective candidate in accelerating diabetic wound healing due to their pro-angiogenic effect. MSCs pretreated with chemistry or biology factors were reported to advance the biological activities of MSC-derived exosomes. Hence, this study was designed to explore whether exosomes derived from human umbilical cord MSCs (hucMSCs) preconditioned with Nocardia rubra cell wall skeleton (Nr-CWS) exhibited superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanisms. The results showed that Nr-CWS-Exos facilitated the proliferation, migration and tube formation of endothelial cells in vitro. In vivo, Nr-CWS-Exos exerted great effect on advancing wound healing by facilitating the angiogenesis of wound tissues compared with Exos. Furthermore, the expression of circIARS1 increased after HUVECs were treated with Nr-CWS-Exos. CircIARS1 promoted the pro-angiogenic effects of Nr-CWS-Exos on endothelial cellsvia the miR-4782-5p/VEGFA axis. Taken together, those data reveal that exosomes derived from Nr-CWS-pretreated MSCs might serve as an underlying strategy for diabetic wound treatment through advancing the biological function of endothelial cells via the circIARS1/miR-4782-5p/VEGFA axis.
Humans ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; Cell Wall Skeleton/metabolism* ; Neovascularization, Physiologic ; Wound Healing/physiology* ; MicroRNAs/metabolism* ; Diabetes Mellitus ; Vascular Endothelial Growth Factor A/metabolism*

Objective:To evaluate the effects of adipose-derived stem cells (ADSCs) and ADM microparticle on diabetic wound healing.Methods:ADSCs was co-cultured with ADM microparticle in vitro. The models of diabetic nude mice were established by intraperitoneal injection of STZ and the full-thickness skin defects were designed on the back. All 24 diabetic mice were randomly divided into 4 group: experimental groups were transplanted with ADSCs and ADM microparticle and the other groups were transplanted with ADSCs, ADM microparticle and blank control group was set up. On the 7th and 14 th days, the wound healing rate of 3 mice randomly selected from each group was calculated, and the thickness between dermis and epidermis was measured by hematoxylin and eosin staining. The density of neovascularization was measured by immunohistochemical staining. The differences were compared between the groups.Results:Compared to the ADSCs groups, the mice of the experimental groups showed higher cell survival rate. The wound healing rate in the experimental groups was (86.0±2.7)% (7 days) and (98.5±1.1)% (14 days), thicker dermis-epidermis distance was (99.1±1.8) μm (7 days) and (124.3±4.3) μm (14 days) ( P<0.05), and higher density of neovascularization was noted. Conclusions:The transplantation with active ADM microparticle can significantly promote neovascularization and wound healing of diabetic wound.

Objective:To probe into the causes, reconstructive strategies, and repair outcomes of asymmetric eyelid configuration after blepharoplasty.Methods:All 73 patients (14 males and 59 females) with asymmetric double eyelid after blepharoplasty were recruited between July 2013 and June 2018 from Department of Plastic and Burns Surgery, West China Hospital, Sichuan University. The patients aged from 18 years to 42 years with the median age of 27 years. The new double eyelid line was designed pre-operation. Releasing subcutaneous adhesion of upper eyelid entirely, trimming inferior orbicularis oculi, adjusting and comparing the attachment position of bilateral levator aponeurosis were performed during surgery. Patients and surgeons marked the appearance of double eyelid both before and after repair operation, results of which were analyzed by t-test.Results:All 73 patients obtained improved double eyelid with primary healing. During follow-up from 8 to 12 months, repaired double eyelid showed satisfactory configuration with smooth natural double eyelid line and symmetric bilateral double eyelid. Of the 73 patients, 3 (4.1%) complaint rough double eyelid line, for whom re-fixation through small incision were adopted and no complication was observed during follow-up time. Scores by patients and surgeons were both significantly better after surgery.Conclusions:Analyzing the causes of asymmetric eyelid after double-eyelid blepharoplasty and repairing it contribute to aesthetic pleasing reconstructed double eyelid.

Objective:To summarize the clinical features, diagnosis and treatment of erythema multiforme caused by Mycoplasma pneumoniae infection.Methods:The data of clinical features, treatment and prognosis of children diagnosed with erythema multiforme caused by Mycoplasma pneumoniae infection and treated in the First Affiliated Hospital of Zhengzhou University from Jane 2016 to December 2019 were retrospectively analyzed, and related literature was summarized.Results:All the 3 patients suffered from fever, cutaneous and mucous membrane lesions.Cutaneous lesions were manifested as exudative erythema multiforme, and the mucous membranes involved included oral mucosa, ocular conjunctiva and genital mucosa.The symptoms in all 3 cases were alleviated after the treatment with glucocor-ticoid, high doses of gamma globulin, anti-Mycoplasma pneumoniae and symptomatic support.Two children suffered secondary infection during treatment and improved with anti-infection.Neither patients had sequelae during the follow-up.Conclusions:Mycoplasma pneumoniae can cause erythema multiforme in children, but it is always misdiagnosed due to its clinical rarity.The mechanism of erythema multiforme caused by Mycoplasma pneumoniae infection is not clear.Early administration of glucocorticoid and high doses of gamma globulin, anti-Mycoplasma pneumoniae and symptomatic support often lead to a good prognosis.

Objective A database of normal people's external nose was established through 3D measurement. This database was used to customize the external nose for patients with nasal defects and to assist the operator to carry out the whole nose reconstruction surgery, so as to carry out the postoperative evaluation.Methods 3D scanning of the subject's face, measurement of relevant indexes of the nose and establishment of a database, the operator used normal nose database to customize the customized external nose for 17 patients with nasal defects, assisted them in the whole nose reconstruction surgery, and used independent sample t test for data statistics to evaluate the expected effect of surgery. Results There was no statistically significant differences between the postoperative actual data and the preoperative personalized data (P> 0.05) in right root wing distance, left root wing distance, nose length, nasal base width, nose width, right side vertical bisect nasal line, left side vertical bisect nasal line, nose height, medial malleolus spacing, face width, mouth split width, facial height, nasal width index, nasal width index, interondylar-nasal width index and nasal high index. The actual data of nasal deep was statistically different from preoperative personalized data (P < 0.05). Conclusions Analysis showed no significant difference between the actual data nasal surgery and preoperative customization data. 3D measurement of normal human external nasal establishment database to customize the external nose for patients with nasal defects, can assist the surgeon to perform total nasal reconstruction surgery and improve predictability and make surgery more precise. Postoperative assessments can also be performed to compare preoperative and postoperative outcomes.